Distinctive histogenesis and immunological microenvironment based on transcriptional profiles of Follicular dendritic cell sarcomas

Claudio Tripodo, Anna Gazzola, Sylvia Hartmann, Silvia Lonardi, Claudia Döring, Claudia Mannu, Maria Rosaria Sapienza, Maria Antonella Laginestra, Valentina Tabanelli, Luisa Lorenzi, Stefano Aldo Pileri, Fabio Fuligni, Federica Melle, Elias Campo, Maura Rossi, Anita Borges, Maura Rossi, Ingrid Simonitsch-Klupp, Carlo Alberto Sagramoso, Jose CabecadasFrancesco Bacci, Claudio Agostinelli, Elena Sabattini, Fabio Facchetti, Alessandro Pileri, Martin-Leo Hansmann, Giovanna Motta, Juan Rosai

Risultato della ricerca: Articlepeer review

10 Citazioni (Scopus)

Abstract

Follicular dendritic cell (FDC) sarcomas are rare mesenchymal tumors with variable clinical, morphologic, and phenotypic characteristics. Transcriptome analysis was performed on multiple FDC sarcomas and compared with other mesenchymal tumors, microdissected Castleman FDCs, and normal fibroblasts. Using unsupervised analysis, FDC sarcomas clustered with microdissected FDCs, distinct from other mesenchymal tumors and fibroblasts. The specific endowment of FDC-related gene expression programs in FDC sarcomas emerged by applying a gene signature of differentially expressed genes (n = 1,289) between microdissected FDCs and fibroblasts. Supervised analysis comparing FDC sarcomas with microdissected FDCs and other mesenchymal tumors identified 370 and 2,927 differentially expressed transcripts, respectively, and on the basis of pathway enrichment analysis ascribed to signal transduction, chromatin organization, and extracellular matrix organization programs. As the transcriptome of FDC sarcomas retained similarity with FDCs, the immune landscape of FDC sarcoma was investigated by applying the CIBERSORT algorithm to FDC sarcomas and non-FDC mesenchymal tumors and demonstrated that FDC sarcomas were enriched in T follicular helper (Tfh) and T regulatory (Treg) cell populations, as confirmed in situ by immunohistochemistry. The enrichment in specific T-cell subsets prompted investigating the mRNA expression of the inhibitory immune receptor PD-1 and its ligands PD-L1 and PD-L2, which were found to be significantly upregulated in FDC sarcomas as compared with other mesenchymal tumors, a finding also confirmed in situ. Here, it is demonstrated for the first time the transcriptional relationship of FDC sarcomas with nonmalignant FDCs and their distinction from other mesenchymal tumors.
Lingua originaleEnglish
pagine (da-a)541-552
Numero di pagine12
RivistaMolecular Cancer Research
Volume15
Stato di pubblicazionePublished - 2017

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Oncology
  • Cancer Research

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